CA2865899A1 - Dual ox40 agonist/il-2 cancer therapy methods - Google Patents
Dual ox40 agonist/il-2 cancer therapy methods Download PDFInfo
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- CA2865899A1 CA2865899A1 CA2865899A CA2865899A CA2865899A1 CA 2865899 A1 CA2865899 A1 CA 2865899A1 CA 2865899 A CA2865899 A CA 2865899A CA 2865899 A CA2865899 A CA 2865899A CA 2865899 A1 CA2865899 A1 CA 2865899A1
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| PCT/US2012/027496 WO2013130102A2 (en) | 2012-03-02 | 2012-03-02 | Dual ox40 agonist/il-2 cancer therapy methods |
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| CA2865899A1 true CA2865899A1 (en) | 2013-09-06 |
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| CA2863818A1 (en) | 2012-02-06 | 2013-08-15 | Brendan CURTI | Cancer treatment and monitoring methods using ox40 agonists |
| EP3116535B1 (en) | 2014-03-12 | 2019-08-07 | CureVac AG | Combination of vaccination and ox40 agonists |
| JP6612252B2 (ja) * | 2014-04-03 | 2019-11-27 | オーガスタ ユニバーシティ リサーチ インスティテュート,インコーポレーテッド | 腫瘍特異的免疫応答の有効性を増強するための方法 |
| EP3148573A4 (en) * | 2014-05-29 | 2017-11-15 | Medimmune, LLC | Ox40l fusion proteins and uses thereof |
| TW201619200A (zh) * | 2014-10-10 | 2016-06-01 | 麥迪紐有限責任公司 | 人類化抗-ox40抗體及其用途 |
| SG10202105879XA (en) | 2014-10-24 | 2021-07-29 | Astrazeneca Ab | Combination |
| ES2937020T3 (es) | 2015-03-03 | 2023-03-23 | Kymab Ltd | Anticuerpos, usos y métodos |
| SG11201708804WA (en) | 2015-05-07 | 2017-11-29 | Agenus Inc | Anti-ox40 antibodies and methods of use thereof |
| US20160347848A1 (en) | 2015-05-28 | 2016-12-01 | Medimmune Limited | Therapeutic combinations and methods for treating neoplasia |
| AU2016364889B2 (en) | 2015-12-02 | 2024-01-04 | Agenus Inc. | Antibodies and methods of use thereof |
| WO2018083248A1 (en) | 2016-11-03 | 2018-05-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
| EP3538152A4 (en) | 2016-11-09 | 2020-09-30 | Agenus Inc. | ANTI-OX40 ANTIBODIES, ANTI-GITR ANTIBODIES, AND PROCESSES FOR USE |
| MA46771A (fr) * | 2016-11-10 | 2021-06-02 | Univ Texas | Méthode de traitement de tumeur immunothérapeutique |
| CN109970864A (zh) * | 2017-12-28 | 2019-07-05 | 上海细胞治疗研究院 | 一种双向激活共刺激分子受体及其用途 |
| TW202028222A (zh) | 2018-11-14 | 2020-08-01 | 美商Ionis製藥公司 | Foxp3表現之調節劑 |
| SG11202108450SA (en) | 2019-02-27 | 2021-09-29 | Ionis Pharmaceuticals Inc | Modulators of malat1 expression |
| EP4037693A1 (en) | 2019-09-30 | 2022-08-10 | Astrazeneca AB | Combination treatment for cancer |
| CN114437228B (zh) * | 2020-10-30 | 2024-02-06 | 中国科学院生物物理研究所 | 一种il-2与抗体亚单位构成的双功能融合蛋白 |
| CN119896729A (zh) * | 2023-10-26 | 2025-04-29 | 南开大学 | 靶向髓系细胞进而增强ox40激动剂抗体药效的药物组合物的药物组合物及其应用 |
Family Cites Families (10)
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|---|---|---|---|---|
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| WO1991010741A1 (en) | 1990-01-12 | 1991-07-25 | Cell Genesys, Inc. | Generation of xenogeneic antibodies |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| US5595756A (en) * | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
| US20030035790A1 (en) * | 1999-01-15 | 2003-02-20 | Shu-Hsia Chen | Combination therapy for the prevention or treatment of cancer, inflammatory disorders or infectious diseases in a subject |
| US20030040477A1 (en) * | 2002-09-23 | 2003-02-27 | Anthony Montgomery | Methods and compositions for modulating t cell activation and uses thereof |
| JP4035579B2 (ja) * | 2003-12-22 | 2008-01-23 | 北海道ティー・エル・オー株式会社 | 標的化t細胞の製造方法及び医薬 |
| US20110008368A1 (en) * | 2006-01-13 | 2011-01-13 | Board Of Regents, The University Of Texas System | Methods of modulating the ox40 receptor to treat cancer |
| GB0620894D0 (en) * | 2006-10-20 | 2006-11-29 | Univ Southampton | Human immune therapies using a CD27 agonist alone or in combination with other immune modulators |
| US8629098B2 (en) * | 2008-01-15 | 2014-01-14 | Yale University | Compositions and methods for adoptive and active immunotherapy |
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- 2012-03-02 AU AU2012371610A patent/AU2012371610A1/en not_active Abandoned
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| EP2819693A2 (en) | 2015-01-07 |
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| WO2013130102A3 (en) | 2014-04-17 |
| AU2012371610A1 (en) | 2014-10-02 |
| HK1205691A1 (en) | 2015-12-24 |
| EP2819693A4 (en) | 2015-10-28 |
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